Combination Therapy for Chronic Hepatitis C Infection

Exclusion Criteria

• •1. Current or prior history of any of the following:
• •* Clinically-significant illness (other than HCV) or any other major medical disorder that may interfere with subject treatment, assessment or compliance with the protocol; subjects currently under evaluation for a potentially clinically-significant illness (other than HCV) are also excluded.
• •* Gastrointestinal disorder or post operative condition that could interfere with the absorption of the study drug.
• •* Poor venous access interfering with required study blood collection.
• •* Clinical hepatic decompensation (i.e., ascites, encephalopathy or variceal hemorrhage).
• •* Solid organ transplantation.
• •* Significant pulmonary disease, significant cardiac disease or porphyria.
• •* Unstable psychiatric disease (Subjects with psychiatric illness that is well-controlled on a stable treatment regimen or currently not requiring medication may be included).
• •* Significant drug allergy (such as anaphylaxis or hepatotoxicity).
• •* Substance abuse, which in the opinion of the investigator is likely to interfere with medication adherence or study compliance.
• •* Lactose allergy, patients with lactose intolerance will be evaluated on a case-by-case basis.
• •2. Positive test results at screening for hepatitis B virus (HBV) surface antigen (HBsAg), HBV DNA (if medically indicated) or anti-HIV antibody (unless previously treated on 13-I-0159).
• •3. Prior exposure to any direct-acting antivirals for HCV infection, except for patients who were previously treated studies 11-I-0258, 13-I-1059 or this study enrolling in Group D.
• •4. History of clinically significant chronic liver disease due to other etiology (e.g., hemochromatosis, autoimmune hepatitis, Wilson s disease, alpha 1-antitrypsin deficiency, alcoholic liver disease, \> moderate non-alcoholic steatohepatitis and toxin exposures).
• •5. Use of herbal/natural remedies for potential benefit to the liver within 21 Days of Day 0.
• •6. History of ascites, variceal hemorrhage, hepatic encephalopathy, or conditions consistent with decompensated liver disease.
• •7. Screening or baseline ECG with clinically significant ECG findings, or a personal/first degree relative history of Torsade de pointes.
• •8. Abnormal hematological and biochemical parameters at screening, including:
• •* Neutrophil count less than 750 cells per cubic millimeter.
• •* Hemoglobin level \< 9 g/dL. If Hgb \< 11g/dL in women and \< 12 g/dL in men other causes of anemia should be excluded as medically indicated.
• •* Platelet count less than or equal to 50,000 cells per cubic millimeter.
• •* Estimated glomerular filtration rate less than 50 milliliter/min/1.73m(2).
• •* ALT or AST level greater than or equal to 10 times upper limit of normal (ULN).
• •* Serum lipase level greater than or equal to 1.5 times upper limit of normal (ULN)at screening or during the screening period in a patient with symptoms consistent with pancreatitis.
• •* Total bilirubin level greater than or equal to 2.0 times upper limit of normal (ULN), except in subjects with Gilbert s syndrome.
• •* Albumin level less than or equal to 3.0 grams per deciliter in patients without cirrhosis, albumin less than or equal to 2.8 g/dL in cirrhotic patients.
• •9. Poorly controlled diabetes mellitus indicated by hemoglobin A1C greater than 9% at screening.
• •10. Donation or loss of blood of greater than 400 milliliter within 8 weeks prior to the first dose of the study drugs.
• •11. Known hypersensitivity to GS-5885, GS-7977, GS-9669, GS-9451 or formulation excipients.
• •12. Pregnant/Breastfeeding women.
• •13. Need for use of the following medications from 21 days prior to the start of study drugs through the end of treatment (unless otherwise specified):
• •* Hematologic stimulating agents (e.g. erythropoiesis-stimulating agents (ESAs); granulocyte colony stimulating factor (GCSF); thrombopoietin (TPO) mimetics).
• •* Chronic systemic immunosuppressants including, but not limited to, corticosteroids (prednisone equivalent of greater than 10 milligrams per day for greater than 2 weeks), azathioprine, or monoclonal antibodies (e.g., infliximab).
• •* Investigational agents or devices for any indication.
• •* Medications for disease conditions excluded from the protocol (e.g., active cancer, transplantation) are not listed under this Concomitant Medication section and are disallowed in the study.
• •* Concomitant use of certain medications or herbal/natural supplements per PI discretion expected to result in pharmacokinetic interactions resulting in increases or decreases in exposure of study drug(s).
• •14. Co-enrollment Guidelines: Co-enrollment in other clinical trials is restricted, other than enrollment in observational studies. Study staff should be notified of co-enrollment status, as it may require prior approval of the investigator.